The overall objective of this research is characterization of the primary incision step in excision repair of human cell DNA. An endonuclease acting selectively on depurinated DNA has been partially purified from human lymphoblasts (CCRF-CEM). This enzyme will be characterized to establish its purity and whether it acts against other types of DNA lesions. Another endonuclease activity which preliminarily acts selectively on ultra-violet light iradiated DNA will be purified further and characterized with respect to other damaged DNA substrates. These enzymes may be used as probes or lesions in DNA, once their specificity and purity is established. Quantitative assay of endonuclease susceptible sites may be used to determine in vivo kinetics of production and repair of specific DNA damage, resulting from treatment with radiation and alkylating agents.